Homogenizing at High Scale in the Laboratory

Few scientists get through a career without homogenizing something, and many of them apply this technique daily. In some cases, and over centuries, scientists made do with a mortar and pestle. That method works, but many of today’s scientists need a high-throughput approach to homogenizing— one that requires more than elbow grease.

Homogenizing makes up a crucial process at Hampton Creek, a San Francisco-based food company where scientists develop novel food products from plant-based proteins. “We have to characterize the food functionality of these proteins,” says Jasmin Hume, lead food chemist at Hampton Creek. For example, many foods must be emulsified, and the resulting products must stay that way. So Hume and her colleagues test how dilute solutions of plant proteins can be emulsified with various amounts of oil, and that requires a homogenization step. “We homogenize the emulsified solutions and then characterize them with light-scattering technology on a different instrument,” Hume says.

Hampton Creek’s discovery platform, which goes by the name Blackbird, will soon be able to automate this process—from homogenization through analysis. In addition to increasing the throughput of the process, the automation will provide reproducibility and increase accuracy. “Destabilization of some emulsions can happen quickly,” Hume explains. So it’s important to control and record the length of the homogenization step, as well as the speed and the time from completing the homogenization to taking the analytical measurement. “This level of control is difficult to accomplish manually, but we expect automation to increase the quality and quantity of data we can produce,” Hume says.

Relative rates

In homogenizing, a rate that qualifies as high throughput varies. “It’s all relative,” says David Shechter, sales manager at BEE International (Chula Vista, CA). In some cases, homogenizing 60 liters in an hour is high throughput; in other situations, that’s just lab scale, which gets increased considerably when the process goes into production. “One thing that is certain,” says Shechter, “industrial rates of homogenizing are high throughput.”

Take a pharmaceutical example. In research and development, scientists will homogenize samples with a lab-size device. If a compound moves to clinical trials, where more samples need to be processed, the company will move to a small production system. If the product gets approved and goes into full-scale production, high-throughput homogenization will be used. “Similar methods of upscaling homogenization occur across other industries,” Shechter says.

Rather than talk about volume, though, some groups consider the number of samples as the key throughput metric. The need for higher homogenizer speed is not just for industry. “We see the need for multi-sample homogenizing requiring high throughput in labs doing genomics or proteomics work, specifically biochemical isolations from all types of tissues,” says Holly Yacko- Archibald, director of sales at PRO Scientific. Those samples, though, will be small and held in microtubes.

To increase the throughput of a homogenizer, most of a device’s features get bigger. The vessel and motor both get larger, and the latter produces more horsepower. “Some companies completely redesign a homogenizer for more throughput,” Shechter notes, but others just make larger versions of smaller ones.

More than a homogenizer is required at high throughput. David Burden, president of OPS Diagnostics (Lebanon, NJ), and his team create customized, high-throughput homogenization solutions for labs. According to Burden, a high-throughput system “implies that at some point the samples will be placed into a liquid handler for processing.” To make a system work at its best, the devices should make a smooth transition from homogenization to liquid handling.

Dealing with DNA

Scientists come to Troemner (Thorofare, NJ) for homogenization related to sample preparations of DNA, RNA, or other aspects of cellular biochemistry. “So, it’s more lysing than homogenizing,” says Jim DeLuca, director of business development at Troemner.

In these applications, scientists homogenize samples to analyze DNA or genomic activity. A scientist might also use this technology when identifying or tagging proteins to study cellular processes. Reproducible studies of such small sample sizes depend on reproducible homogenization. To accomplish that, a Troemner homogenizer uses a linear motion, rather than moving a sample in a figure eight or a more complicated pattern. “This produces really effective grinding and pulverization,” says DeLuca. “The result is very homogenous across all samples, such as each one in a 96-well plate.”

Homogenizer help

As Burden says, “When someone is looking to purchase a homogenizer, the primary question should not be about the homogenizer, but rather: What are the needs of the process?” Start by working on the process at a smaller scale to find any problems. “In this process design, noting where bottlenecks occur is critical, as it can greatly influence what type of homogenizer will be needed,” Burden says. “Map out the steps from sample collection to analyte extraction and estimate the time and costs for all the steps.” Then, you’re ready to select the best homogenizer.

The homogenizer that works best for your lab probably depends on what you will be homogenizing and what you will do with the samples. “Not all high-throughput systems can properly homogenize all types of samples,” says Archibald. “You should look at the type of homogenizing technology you are using now and try and stay with that.”

The cost will also factor into your decision, and the range is wide. In fact, Archibald calls the range “huge.” As she notes, you can purchase “a basic multipack of probes and a kit for $2,000–$3,000, a mid-range multi-sample system for $9,000– $12,000, or a fully robotic homogenization system for around $50,000–$100,000.”

As you think about upgrading from a mortar and pestle—or whatever homogenizing system is being used in your lab now—ask yourself: How much homogenizer power will it take to break the bottleneck in my lab? If homogenizing one sample at a time works for you, keep putting that pestle to work. Otherwise, see how much throughput it will take to up the game in your lab. It might not be the sexiest platform in your lab—okay, so it is surely not!—but getting the right grind matters for more than coffee.